"I've been lucky in that I've always worked with writers whose voices are so specific that there really isn't any way to recalibrate things without them being intimately involved," says Steven Soderbergh as he swivels in a chair in the happily cluttered New York loft space that doubles as his office and painting studio. On this particular morning, one of those writers, Scott Z. Burns, is seated to Soderbergh's left, ready to join the discussion of Side Effects, the devilish psychological thriller that marks Burns' third collaboration with the director, following the whistle-blower farce The Informant! (2009) and the all-star virus drama Contagion (2011), where prominent billing was no guarantee of any cast member's survival. It is also the film Soderbergh has announced will be his last for the big screen, as he embarks on his "retirement," which is really just a shifting of creative gears (into painting, theater, and possibly long-form television).

In Side Effects, a tattoo-free Rooney Mara plays Emily Taylor, a young bride whose joy over the imminent parole of her insider-trading husband (Channing Tatum) is offset by the return of her crippling depression. Enter a shrink (Jude Law) who takes Emily as a patient, setting into motion one of the most deliciously knotted series of twists this side of Body Heat. Inspired by research Burns did at Bellevue while working as a writer on the short-lived ABC series Wonderland, as well as by his love of film noirs like Double Indemnity. Like their previous films together, this one was a true creative partnership, in which Burns remained a key long after he had finished the script.

VILLAGE VOICE: So, you're on set every day during?

SCOTT Z. BURNS: Yes.

STEVEN SODERBERGH: And he sees every cut, every iteration, any idea that I have. And he's always got his own ideas. The problem becomes when you have somebody on set who's basically functioning as a security force to protect every little thing they wrote. That's a problem, because when stuff's in front of you, you need to respond and tweak things. But I've never had that.

BURNS: Early on during The Informant!, I remember Matt [Damon] and I were having a conversation about some scene—it was the second or third day of shooting—when I thought, "Oh, this is probably not cool that I'm doing this." I got to set and I said to [producer Gregory Jacobs], "I hope I didn't overstep my bounds, but Matt had a question..." I think I blamed it on Matt. And either Greg or Steven said to me, "Well, that's why you're here. You're here because you know the story better than any of us."

VOICE: Steven, you've said that for Contagion you established ground rules (e.g., no helicopter shots) to avoid falling into traps of the disaster-movie genre. Were there any similar rules for Side Effects vis-à-vis the thriller genre?

SODERBERGH: I don't feel like there were as many, because I guess I looked at Contagion as a horror film more than a disaster film. So I wanted to avoid the tropes of disaster movies that I always felt made them generic. We wanted it to be really intimate. We wanted you to be inside the experience, to never leave this handful of characters. So in post we did a lot of rethinking to maintain that kind of focus.

BURNS: I feel like you had some rules about how you treated New York in Side Effects.

SODERBERGH: It's true, mostly because what are you going to do that hasn't been done by Sidney Lumet or Alan Pakula or Martin Scorsese or Spike Lee? What I decided was: I'm not going to do a New York montage. The only time I'm going to show an establishing shot is when, if I didn't show it, you wouldn't know where you are and would be confused. We also wanted the movie to be as lean as possible. My attitude was: if you took one shot out, the movie would be diminished; if you added one shot, it would be fat. During post, Scott would send me e-mails saying, "I don't think we need those two lines at the beginning of that scene."

VOICE: That reminds me of something I heard Walter Hill say: "I believe in brevity of statement." He was referring to the great studio directors like John Ford and Raoul Walsh, who felt that each shot in a movie should somehow advance the story, But most movies today are full of fat and much too long. Who's to blame for that?

SODERBERGH: The bottom line is that, on most movies, nobody in the chain is thinking in those terms. They're thinking only in terms of immediate effect. I wonder sometimes: Is this fallout from electronic editing, which allows you to try everything, and can result, I think, in movies being very fine-tuned on a micro level, but very shoddy on a macro level? One of the things that I do when we're editing is, three or four times a week I watch the whole film from beginning to end. Nothing will cure you faster of being in love with your own stuff than that. I'm a big believer that every time you use a close-up, for example, you potentially diminish the power of the next one you're going to use. So I try to be very careful about when we start moving in. And then when you go in, there are choices to be made about how you go in. You'll notice in terms of Rooney and how her face is, I like to be above her a lot, because she's got a very interesting angularity. Also, psychologically, it works, because there are issues in terms of how she's putting information out there, so to continually have the camera right at eye level wouldn't be serving her character.

VOICE: Side Effects engages with Big Pharma's highly effective grip on the American popular imagination.

BURNS: Depression is a thing that really exists, and so is sadness. But those are two different things, and sadness can be a very well-reasoned response to a set of circumstances around you. Depression is a debilitating syndrome that is persistent. But if you're sad, you certainly don't want to stay there, and you don't want to get depressed, so why not take the pill that seems to solve the even bigger problem? When the people watching those commercials aren't all that educated about those things, and you see someone who looks like you staring out a window or sitting on a park bench being sad and everyone else is running around with a balloon, you want to be with the balloons.